Iloprost Improves Ventricular Function in the Hypertrophic and Functionally Impaired Right Heart by Direct Stimulation

Abstract

Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; n = 8), pulmonary trunk banding (PTB; n = 8), or a sham operation (n = 8). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a 12% ± 4% (P = 0.022) increase in stroke volume in the sham group and a 12% ± 3% (P = 0.005) increase in the PTB group. RV dP=dtmax was elevated by 11% ± 5% (P = 0.039) in the sham group and by 12% ± 3% (P = 0.016) in the PTB group. An elevation in cardiac output of 14% ±3% (P = 0.0008) and an 11% ± 2% (P = 0.0021) increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

The Pulmonary Vascular Research Institute (PVRI) is a registered Charity in the United Kingdom (Charity No: 1127115) and a private limited company by guarantee. The company registration number in the United Kingdom is 5780068.